We plan to investigate two broad aspects of iron deficiency. The first group of experiments involves the manifestations of iron deficiency that relate to energy metabolism, work performance, and the production of the iron containing enzymes of skeletal muscle. These interrelated studies will use the iron deficient rat as an experimental model. The metabolic studies will pursue the hypothesis that iron deficiency many result in an increased rate of glycolysis as a means of adapting to a low oxidative capacity; this might occur by increased recycling of lactate to glucose via the Cori and/or the Glucose-Alanine Cycle. These studies will utilize radio-actively labeled glucose, lactate, and alanine administered to rats in a metabolic chamber designed to take measurements during rest and exercise. Studies of work performance will explore the effectiveness of adaptive mechanisms to maintain performance in "sprint" and "endurance" types of exercise with iron deficiency of increasing severity; in addition, the effects of prior exercise training will be determined. Biochemical studies will focus on the iron-sulfur enzymes of skeletal muscle mitochondria which we hypothesize are rate-limiting to the oxidative metabolism of skeletal muscle in iron deficiency. The second group of studies involves the interactions between iron deficiency and infection. Our study is to be integrated with a large field trial of an H. influenzae b polysaccharide-diphtheria toxoid conjugate vaccine among Native Americans in Alaska, a population that has an unusually high prevalence of both infections and iron responsive anemia. Analyses will include data on morbidity and breast feeding and measurements of specific antibody, hemoglobin, and serum ferritin in an estimated 2000 children below 2 years of age. The results should indicate whether frequent infections are a major factor predisposing to iron deficiency and, secondly, whether iron deficiency can be responsible for an impaired immune response and increased infections. A second population in Sweden should provide more detailed information on what types of common infections are associated with the anemia of inflammatory disease. Both the rat and human studies are intended to further our understanding of the pathogenesis of iron deficiency and to identify the best strategies for its prevention.